Alcohol-induced pancreatitis is often characterized by repeated flares of acute pancreatitis and the eventual development of exocrine and endocrine pancreatic failure. Once chronic pancreatitis develops, there is no established way to predictably slow down the progression of the disease. In preliminary studies, it has been observed that a substantial proportion of subjects with alcohol-induced pancreatitis have biliary microlithiasis. Biliary microlithiasis has been implicated as a cause of idiopathic acute recurrent pancreatitis. Based on the preliminary observations and the known role of biliary microlithiasis in pancreatitis, it is hypothesized biliary [unreadable] microlithiasis is frequently present in subjects with alcohol-induced pancreatitis and that its dissolution with urosodeoxycholic acid (UDCA) will ameliorate the acute flares of pancreatitis and slow down the progression to pancreatic failure. This R21 exploratory grant proposal represents the first step towards testing this novel hypothesis and has two major objectives: (1) to define the prevalence and types of biliary microlithiasis in subjects with alcohol-induced pancreatitis, and (2) to provide "proof of concept" that UDCA can clear the bile of microlithiasis in subjects with alcohol-induced pancreatitis and identify the factors associated with successful clearance of microlithiasis. [unreadable] [unreadable] These will be accomplished by studies with two specific aims: (1) to define the prevalence and types of biliary microlithiasis in subjects with alcohol-induced pancreatitis and (2) to perform a PHASE II pilot study of UDCA (10 mg/kg/day) to define its biologic effectiveness for clearance of microlithiasis in subjects with alcohol-induced pancreatitis and biliary microlithiasis. This will be accomplished using a double-blind, placebo-controlled, randomized study design. The primary endpoint will be the absence of biliary microlithiasis, defined by microscopic examination of bile obtained from the duodenum after cholecystokinin injection at study termination at 6 months. Secondary endpoints will include (1) subset analysis to identify which types of microlithiasis are dissolved by UDCA, (2) identify factors associated with dissolution of microlithiasis, (3) changes in bile composition over time, (4) frequency of flares of pancreatitis, and (4) the tolerability of UDCA, Axcan Pharma, has kindly agreed to provide the drug and placebo free of cost to the study. The long-term goal is to use data from this R21 proposal to develop a RO1 proposal about a large scale phase III clinical trial of UDCA for alcohol-induced pancreatitis. [unreadable] [unreadable] [unreadable]